Project Summary: Overview: Depression affects more than 16 million American adults and more than half of all depression patients do not respond to medication. Transcranial magnetic stimulation (TMS) is an important anti- depressant treatment option that targets specific brain circuits responsible for mood and behavior. TMS efficacy and risk is strongly linked to correct TMS coil placement and can be significantly improved by accurate neuronavigation. We propose a mixed reality TMS neuronavigation setup that integrates TMS coil and patient tracking, visualization of brain anatomy and targeting feedback and neuronavigation controls in a single immersive environment. Relevance: While neuronavigation is used in certain research settings, the high cost and added time and effort for the operator lead to a very slow adoption at most TMS sites. A low cost mixed-reality TMS neuronavigation system that is easy-to-use could promote much more widespread dissemination of neuronavigation capabilities, thereby improving treatment outcomes and reducing risk to the patient. Approach: We will develop an advanced MRI protocol designed to visualize and locate brain anatomy and integrate electric field models for predicting optimal TMS coil positioning. We will optimize the use of an RGBD camera for tracking the TMS coil and the patient's head. We will test coil positioning on 20 healthy volunteers using the mixed reality and conventional desktop neuronavigation systems. Summary: This proposal aims to create a new radiological paradigm where mixed reality is used to merge medical imaging data with the real world to guide the TMS practitioner during treatment of depression. The mixed reality setup will be tested against a desktop neuronavigation device with the aim of demonstrating improved targeting speed and training performance and matched accuracy and consistency. The mixed reality neuronavigation system will provide an improved and streamlined user experience, enabling a wide-spread use of neuronavigation. Our research team includes world-class experts in radiology, virtual and augmented reality and psychiatry.